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Catabolism and biotechnological applications of cholesterol degrading bacteria.

García JL, Uhía I, Galán B - Microb Biotechnol (2012)

Bottom Line: Cholesterol is a steroid commonly found in nature with a great relevance in biology, medicine and chemistry, playing an essential role as a structural component of animal cell membranes.The ubiquity of cholesterol in the environment has made it a reference biomarker for environmental pollution analysis and a common carbon source for different microorganisms, some of them being important pathogens such as Mycobacterium tuberculosis.This work revises the accumulated biochemical and genetic knowledge on the bacterial pathways that degrade or transform this molecule, given that the characterization of cholesterol metabolism would contribute not only to understand its role in tuberculosis but also to develop new biotechnological processes that use this and other related molecules as starting or target materials.

View Article: PubMed Central - PubMed

Affiliation: Environmental Biology Department, Centro de Investigaciones Biológicas, CSIC, C/ Ramiro de Maeztu, 9, 28040 Madrid, Spain. jlgarcia@cib.csic.es

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Organization of the main gene clusters implied or suggested to be involved in the degradation of cholesterol in M. smegmatis mc2155. The identity number for each MSMEG gene is indicated within the arrows. The name of some genes of interest is written above them. Numbers below genes indicate the number of bp between adjacent genes; numbers in brackets indicate separation and numbers in parentheses indicate overlap. Numbers above diagonal lines indicate the genomic position in kb. Orange: mce cluster. Green: genes suggested and/or proved to participate in the side‐chain degradation. Blue: genes suggested and/or proved to participate in the central or lower catabolic pathway. Yellow: genes coding the transcriptional repressors KstR and KstR2. Genes surrounded by a dashed line are controlled by KstR2, the rest of the genes showed in this figure are controlled by KstR (except for MSMEG_5905, 5909, 5910, 5912, 5916, 5917, 5924, 5926, 5928, 5936, 5938, 6005, 6006, 6007, 6010, 6034, which could not be proved to be controlled by any of both repressors) (Kendall et al., 2007; 2010; Uhía et al., 2012).
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f4: Organization of the main gene clusters implied or suggested to be involved in the degradation of cholesterol in M. smegmatis mc2155. The identity number for each MSMEG gene is indicated within the arrows. The name of some genes of interest is written above them. Numbers below genes indicate the number of bp between adjacent genes; numbers in brackets indicate separation and numbers in parentheses indicate overlap. Numbers above diagonal lines indicate the genomic position in kb. Orange: mce cluster. Green: genes suggested and/or proved to participate in the side‐chain degradation. Blue: genes suggested and/or proved to participate in the central or lower catabolic pathway. Yellow: genes coding the transcriptional repressors KstR and KstR2. Genes surrounded by a dashed line are controlled by KstR2, the rest of the genes showed in this figure are controlled by KstR (except for MSMEG_5905, 5909, 5910, 5912, 5916, 5917, 5924, 5926, 5928, 5936, 5938, 6005, 6006, 6007, 6010, 6034, which could not be proved to be controlled by any of both repressors) (Kendall et al., 2007; 2010; Uhía et al., 2012).

Mentions: Our knowledge of genes involved in microbial degradation of cholesterol side‐chain is still very limited, but a catabolic gene cluster was identified in R. jostii RHA1 and Mycobacterium smegmatis, encoding several enzymes predicted to be involved in the β‐oxidation process (van der Geize et al., 2007; Uhía et al., 2012) (Fig. 4). Recently, the fadD19 gene product of this cluster has been identified as a steroid‐CoA ligase with an essential role in the degradation of C‐24 branched‐chain‐sterols (Wilbrink et al., 2011). In addition, the fadA5 (Rv3546) gene from M. tuberculosis H37Rv has been proposed to encode a β‐ketoacyl‐CoA thiolase that functions in cholesterol side‐chain β‐oxidation (Nesbitt et al., 2010). This gene is upregulated by cholesterol and repressed by KstR (see below), and is required for utilization of cholesterol as a sole carbon source in vitro and for full virulence of M. tuberculosis in the chronic stage of mouse lung infection (Nesbitt et al., 2010).


Catabolism and biotechnological applications of cholesterol degrading bacteria.

García JL, Uhía I, Galán B - Microb Biotechnol (2012)

Organization of the main gene clusters implied or suggested to be involved in the degradation of cholesterol in M. smegmatis mc2155. The identity number for each MSMEG gene is indicated within the arrows. The name of some genes of interest is written above them. Numbers below genes indicate the number of bp between adjacent genes; numbers in brackets indicate separation and numbers in parentheses indicate overlap. Numbers above diagonal lines indicate the genomic position in kb. Orange: mce cluster. Green: genes suggested and/or proved to participate in the side‐chain degradation. Blue: genes suggested and/or proved to participate in the central or lower catabolic pathway. Yellow: genes coding the transcriptional repressors KstR and KstR2. Genes surrounded by a dashed line are controlled by KstR2, the rest of the genes showed in this figure are controlled by KstR (except for MSMEG_5905, 5909, 5910, 5912, 5916, 5917, 5924, 5926, 5928, 5936, 5938, 6005, 6006, 6007, 6010, 6034, which could not be proved to be controlled by any of both repressors) (Kendall et al., 2007; 2010; Uhía et al., 2012).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3815891&req=5

f4: Organization of the main gene clusters implied or suggested to be involved in the degradation of cholesterol in M. smegmatis mc2155. The identity number for each MSMEG gene is indicated within the arrows. The name of some genes of interest is written above them. Numbers below genes indicate the number of bp between adjacent genes; numbers in brackets indicate separation and numbers in parentheses indicate overlap. Numbers above diagonal lines indicate the genomic position in kb. Orange: mce cluster. Green: genes suggested and/or proved to participate in the side‐chain degradation. Blue: genes suggested and/or proved to participate in the central or lower catabolic pathway. Yellow: genes coding the transcriptional repressors KstR and KstR2. Genes surrounded by a dashed line are controlled by KstR2, the rest of the genes showed in this figure are controlled by KstR (except for MSMEG_5905, 5909, 5910, 5912, 5916, 5917, 5924, 5926, 5928, 5936, 5938, 6005, 6006, 6007, 6010, 6034, which could not be proved to be controlled by any of both repressors) (Kendall et al., 2007; 2010; Uhía et al., 2012).
Mentions: Our knowledge of genes involved in microbial degradation of cholesterol side‐chain is still very limited, but a catabolic gene cluster was identified in R. jostii RHA1 and Mycobacterium smegmatis, encoding several enzymes predicted to be involved in the β‐oxidation process (van der Geize et al., 2007; Uhía et al., 2012) (Fig. 4). Recently, the fadD19 gene product of this cluster has been identified as a steroid‐CoA ligase with an essential role in the degradation of C‐24 branched‐chain‐sterols (Wilbrink et al., 2011). In addition, the fadA5 (Rv3546) gene from M. tuberculosis H37Rv has been proposed to encode a β‐ketoacyl‐CoA thiolase that functions in cholesterol side‐chain β‐oxidation (Nesbitt et al., 2010). This gene is upregulated by cholesterol and repressed by KstR (see below), and is required for utilization of cholesterol as a sole carbon source in vitro and for full virulence of M. tuberculosis in the chronic stage of mouse lung infection (Nesbitt et al., 2010).

Bottom Line: Cholesterol is a steroid commonly found in nature with a great relevance in biology, medicine and chemistry, playing an essential role as a structural component of animal cell membranes.The ubiquity of cholesterol in the environment has made it a reference biomarker for environmental pollution analysis and a common carbon source for different microorganisms, some of them being important pathogens such as Mycobacterium tuberculosis.This work revises the accumulated biochemical and genetic knowledge on the bacterial pathways that degrade or transform this molecule, given that the characterization of cholesterol metabolism would contribute not only to understand its role in tuberculosis but also to develop new biotechnological processes that use this and other related molecules as starting or target materials.

View Article: PubMed Central - PubMed

Affiliation: Environmental Biology Department, Centro de Investigaciones Biológicas, CSIC, C/ Ramiro de Maeztu, 9, 28040 Madrid, Spain. jlgarcia@cib.csic.es

Show MeSH
Related in: MedlinePlus